大黄对高氧致新生大鼠支气管肺发育不良的影响

Effect of rhubarb on neonatal rats with bronchopulmonary dysplasia induced by hyperoxia

摘要:

目的 探讨大黄对高氧致新生大鼠支气管肺发育不良（BPD）的影响。方法 将64只生后4 d大鼠随机分成空气对照组、大黄对照组、高氧模型组和高氧+大黄组（n=16）。大鼠暴露于60%氧浓度中构建BPD模型。造模同时，两个大黄干预组每天给予600 mg/kg大黄提取物混悬液灌胃1次。各组大鼠于生后14 d、21 d，苏木精-伊红（HE）染色观察肺组织形态学改变；分光光度计法检测丙二醛（MDA）水平及超氧化物歧化酶（SOD）活性；RT-PCR、Western blot法检测肺组织中TNF-α、IL-6 mRNA和蛋白表达水平。结果 高氧模型组大鼠肺组织出现肺泡数目减少、体积增大、结构简单化等发育受阻的表现，并随高氧暴露时间的延长损伤加重；高氧+大黄组大鼠肺组织病理改变明显减轻。大鼠生后14 d及21 d，与两对照组相比，高氧模型组放射状肺泡计数（RAC）明显减少，肺组织中SOD活性降低，MDA水平、TNF-α mRNA及蛋白水平、IL-6 mRNA及蛋白水平均升高（P < 0.05）。与高氧模型组相比，高氧+大黄组RAC明显增加，肺组织中SOD活性升高，MDA水平、TNF-α mRNA及蛋白水平、IL-6 mRNA及蛋白水平均降低（P < 0.05）。结论 大黄可能通过抑制炎症和氧化应激反应对高氧致新生大鼠BPD发挥保护作用。

Abstract:

Objective To study the effect of rhubarb on neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia. Methods A total of 64 rats (postnatal day 4) were randomly divided into four groups:air control, rhubarb control, hyperoxia model, and hyperoxia+rhubarb (n=16 each). The rats in the hyperoxia model and hyperoxia+rhubarb groups were exposed to hyperoxia (60% O₂) to establish a BPD model. The rats in the rhubarb control and hyperoxia+rhubarb groups were given rhubarb extract suspension (600 mg/kg) by gavage daily. The pathological changes of lung tissue were evaluated by hematoxylin-eosin staining on postnatal days 14 and 21. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by spectrophotometry. The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined by RT-PCR and Western blot respectively. Results The hyperoxia model group showed reduced alveolar number, increased alveolar volume, and simplified alveolar structure, which worsened over the time of exposure to hyperoxia. These pathological changes were significantly reduced in the hyperoxia+rhubarb group. On postnatal days 14 and 21, compared with the air control and rhubarb control groups, the hyperoxia model group had significantly reduced radical alveolar count (RAC), significantly reduced activity of SOD in the lung tissue, and significantly increased content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P < 0.05). Compared with the hyperoxia model group, the hyperoxia+rhubarb group had significantly increased RAC, significantly increased activity of SOD in the lung tissue, and significantly reduced content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P < 0.05). Conclusions Rhubarb may play a protective role in rats with BPD induced by hyperoxia through inhibiting inflammatory response and oxidative stress.